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Pharmaceutics Jun 2024Natural compounds such as polyphenols play several positive roles in maintaining the oxidative and inflammatory capacity of cells, which leads to their potential use as... (Review)
Review
Natural compounds such as polyphenols play several positive roles in maintaining the oxidative and inflammatory capacity of cells, which leads to their potential use as anticancer therapeutics. There is promising evidence for the in vitro and in vivo anticancer activity of many polyphenols, including resveratrol and quercetin, specifically in the treatment of colorectal cancer (CRC). There is a clear association between resveratrol and quercetin in interfering with the mechanistic pathways involved in CRC, such as Wnt, P13K/AKT, caspase-3, MAPK, NF-κB, etc. These molecular pathways establish the role of resveratrol and quercetin in controlling cancer cell growth, inducing apoptosis, and inhibiting metastasis. The major bottleneck in the progression of the use of resveratrol and quercetin as anticancer therapeutics is their reduced bioavailability in vivo because of their rapid metabolism in humans. Recent advancements in various nanotechnological formulations are promising for overcoming these bioavailability issues. Various nanoformulations of resveratrol and quercetin have shown an optimistic impact on reducing the solubility and improving the stability of resveratrol and quercetin in vivo. A combinatorial approach using nanoformulations of resveratrol with quercetin could potentially increase the impact of resveratrol in controlling CRC cell proliferation. This review discusses the mechanism of resveratrol and quercetin, the two bioactive polyphenolics, in colon cancer, with an emphasis on various types of nanoformulations of the two molecules targeting colon cancer. It also explores the synergistic effect of combining resveratrol and quercetin in various nanoformulations, targeting colon cancer. This research delves into the enhanced pharmacokinetics and potential chemotherapeutic benefits of these bioactive polyphenolics when used together in innovative ways.
PubMed: 38931884
DOI: 10.3390/pharmaceutics16060761 -
Pharmaceutics Jun 2024HER2-targeting therapies have advanced breast cancer treatment over the past decade. Clinically, eligibility for HER2 therapies is determined by assessing HER2 levels on...
HER2-targeting therapies have advanced breast cancer treatment over the past decade. Clinically, eligibility for HER2 therapies is determined by assessing HER2 levels on tumor cell surfaces through immunohistochemistry or by gene regulation through fluorescence in situ hybridization. HER2 therapies are not always effective in patients with elevated levels of HER2, questioning whether the amount of HER2 is sufficiently predictive of patient outcomes. Additionally, the HER2-targeting antibody-drug conjugate (ADC) Enhertu was recently approved for metastasized HER2-low cancers, confirming the benefits of HER2 treatment for patients with low HER2 levels. To evaluate the correlation between HER2 levels and treatment efficacy, we quantified HER2 on eight cell lines using flow cytometry while simultaneously determining the toxicity of two HER2-targeting ADCs. Both HER2-high cell lines and HER2-low cell lines had significant toxicity responses to ADCs. We quantified HER2 internalization and found no correlation between HER2 levels and the percentage of internalization. We found a useful metric suggesting that a minimum number of HER2 receptors trafficked to lysosomes is sufficient to provide effective treatment. Our results indicate that the current standards of determining eligibility for HER2 therapy could limit patients' access to effective treatment. In conclusion, HER2 levels are not wholly adequate to determine the response to ADC treatment.
PubMed: 38931874
DOI: 10.3390/pharmaceutics16060752 -
Pharmaceutics May 2024Astatine-211 (At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in... (Review)
Review
Astatine-211 (At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in vivo stability of At-labeled radiopharmaceuticals remains a major challenge. This review provides a comprehensive overview of the current strategies for At radiolabeling, including nucleophilic and electrophilic substitution reactions, as well as the recent advances in the development of novel bifunctional coupling agents and labeling approaches to enhance the stability of At-labeled compounds. The preclinical and clinical applications of At-labeled radiopharmaceuticals, including small molecules, peptides, and antibodies, are also discussed. Looking forward, the identification of new molecular targets, the optimization of At production and quality control methods, and the continued evaluation of At-labeled radiopharmaceuticals in preclinical and clinical settings will be the key to realizing the full potential of At-based targeted alpha therapy. With the growing interest and investment in this field, At-labeled radiopharmaceuticals are poised to play an increasingly important role in future cancer treatment.
PubMed: 38931860
DOI: 10.3390/pharmaceutics16060738 -
Pharmaceutics May 2024Combining immune checkpoint inhibitors, specifically nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4), holds substantial promise in revolutionizing cancer treatment.... (Review)
Review
Combining immune checkpoint inhibitors, specifically nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4), holds substantial promise in revolutionizing cancer treatment. This review explores the transformative impact of these combinations, emphasizing their potential for enhancing therapeutic outcomes across various cancers. Immune checkpoint proteins, such as PD1 and CTLA4, play a pivotal role in modulating immune responses. Blocking these checkpoints unleashes anticancer activity, and the synergy observed when combining multiple checkpoint inhibitors underscores their potential for enhanced efficacy. Nivolumab and ipilimumab harness the host's immune system to target cancer cells, presenting a powerful approach to prevent tumor development. Despite their efficacy, immune checkpoint inhibitors are accompanied by a distinct set of adverse effects, particularly immune-related adverse effects affecting various organs. Understanding these challenges is crucial for optimizing treatment strategies and ensuring patient well-being. Ongoing clinical trials are actively exploring the combination of checkpoint inhibitory therapies, aiming to decipher their synergistic effects and efficacy against diverse cancer types. This review discusses the mechanisms, adverse effects, and various clinical trials involving nivolumab and ipilimumab across different cancers, emphasizing their transformative impact on cancer treatment.
PubMed: 38931856
DOI: 10.3390/pharmaceutics16060732 -
Pharmaceutics May 2024Fluoropyrimidine (FP) drugs are central components of combination chemotherapy regimens for the treatment of colorectal cancer (CRC). FP-based chemotherapy has improved... (Review)
Review
Fluoropyrimidine (FP) drugs are central components of combination chemotherapy regimens for the treatment of colorectal cancer (CRC). FP-based chemotherapy has improved survival outcomes over the last several decades with much of the therapeutic benefit derived from the optimization of dose and delivery. To provide further advances in therapeutic efficacy, next-generation prodrugs and nanodelivery systems for FPs are being developed. This review focuses on recent innovative nanodelivery approaches for FP drugs that display therapeutic promise. We summarize established, clinically useful FP prodrug strategies, including capecitabine, which exploit tumor-specific enzyme expression for optimal anticancer activity. We then describe the use of FP DNA-based polymers (e.g., CF10) for the delivery of activated FP nucleotides as a nanodelivery approach with proven activity in pre-clinical models and with clinical potential. Multiple nanodelivery systems for FP delivery show promise in CRC pre-clinical models and we review advances in albumin-mediated FP delivery, the development of mesoporous silica nanoparticles, emulsion-based nanoparticles, metal nanoparticles, hydrogel-based delivery, and liposomes and lipid nanoparticles that display particular promise for therapeutic development. Nanodelivery of FPs is anticipated to impact CRC treatment in the coming years and to improve survival for cancer patients.
PubMed: 38931855
DOI: 10.3390/pharmaceutics16060734 -
Pharmaceutics May 2024This research underscores the potential of combining nanotechnology with conventional therapies in cancer treatment, particularly for challenging cases like pancreatic...
This research underscores the potential of combining nanotechnology with conventional therapies in cancer treatment, particularly for challenging cases like pancreatic cancer. We aimed to enhance pancreatic cancer treatment by investigating the synergistic effects of gold nanoparticles (GNPs) and docetaxel (DTX) as potential radiosensitizers in radiotherapy (RT) both in vitro and in vivo, utilizing a MIA PaCa-2 monoculture spheroid model and NRG mice subcutaneously implanted with MIA PaCa-2 cells, respectively. Spheroids were treated with GNPs (7.5 μg/mL), DTX (100 nM), and 2 Gy of RT using a 6 MV linear accelerator. In parallel, mice received treatments of GNPs (2 mg/kg), DTX (6 mg/kg), and 5 Gy of RT (6 MV linear accelerator). In vitro results showed that though RT and DTX reduced spheroid size and increased DNA DSBs, the triple combination of DTX/RT/GNPs led to a significant 48% ( = 0.05) decrease in spheroid size and a 45% ( = 0.05) increase in DNA DSBs. In vivo results showed a 20% ( = 0.05) reduction in tumor growth 20 days post-treatment with (GNPs/RT/DTX) and an increase in mice median survival. The triple combination exhibited a synergistic effect, enhancing anticancer efficacy beyond individual treatments, and thus could be employed to improve radiotherapy and potentially reduce adverse effects.
PubMed: 38931837
DOI: 10.3390/pharmaceutics16060713 -
Sensors (Basel, Switzerland) Jun 2024Arsenic, existing in various chemical forms such as arsenate (As(V)) and arsenite (As(III)), demands serious attention in water and environmental contexts due to its... (Review)
Review
Arsenic, existing in various chemical forms such as arsenate (As(V)) and arsenite (As(III)), demands serious attention in water and environmental contexts due to its significant health risks. It is classified as "carcinogenic to humans" by the International Agency for Research on Cancer (IARC) and is listed by the World Health Organization (WHO) as one of the top 10 chemicals posing major public health concerns. This widespread contamination results in millions of people globally being exposed to dangerous levels of arsenic, making it a top priority for the WHO. Chronic arsenic toxicity, known as arsenicosis, presents with specific skin lesions like pigmentation and keratosis, along with systemic manifestations including chronic lung diseases, liver issues, vascular problems, hypertension, diabetes mellitus, and cancer, often leading to fatal outcomes. Therefore, it is crucial to explore novel, cost-effective, and reliable methods with rapid response and improved sensitivities (detection limits). Most of the traditional detection techniques often face limitations in terms of complexity, cost, and the need for sophisticated equipment requiring skilled analysts and procedures, which thereby impedes their practical use, particularly in resource-constrained settings. Colorimetric methods leverage colour changes which are observable and quantifiable using simple instrumentation or even visual inspection. This review explores the colorimetric techniques designed to detect arsenite and arsenate in water. It covers recent developments in colorimetric techniques, and advancements in the role of nanomaterials in colorimetric arsenic detection, followed by discussion on current challenges and future prospects. The review emphasizes efforts to improve sensitivity, selectivity, cost, and portability, as well as the role of advanced materials/nanomaterials to boost the performance of colorimetric assays/sensors towards combatting this pervasive global health concern.
Topics: Colorimetry; Arsenic; Nanostructures; Humans; Water Pollutants, Chemical; Water
PubMed: 38931673
DOI: 10.3390/s24123889 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves... (Review)
Review
BACKGROUND
Ovarian cancer (OC) is a significant cause of cancer-related mortality in women globally, with a five-year survival rate of approximately 49%. Standard therapy involves cytoreductive surgery followed by chemotherapy. Its poor prognosis has driven interest in alternative therapies such as targeted molecular agents like bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi).
MATERIALS AND METHODS
This review systematically searched PubMed from January 2018 to December 2023 for studies on PARPi in OC. Emphasis was on identifying relevant Phase III trials, extracting data on study design, patient demographics, and outcomes. Special focus was on assessing PARPi efficacy, safety, impact on quality of life, and ongoing trials, including those on Clinicaltrials.gov.
RESULTS
The efficacy of PARPi in first-line therapy for OC has been extensively studied. Trials like SOLO-1, PRIMA, and ATHENA-MONO have demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in patients with BRCA mutations. Additionally, the combination of PARPi with other agents like bevacizumab has shown promising results in extending PFS. However, PARPi treatment is associated with various adverse effects, including hematologic toxicities like anemia, thrombocytopenia, and neutropenia. While most adverse events are manageable, some patients may require dose adjustments or discontinuation of treatment. Importantly, PARPi maintenance therapy has not adversely affected health-related quality of life (HRQoL), with studies reporting similar HRQoL scores between PARPi-treated and placebo-treated patients.
CONCLUSIONS
PARPi offer effective treatment with manageable side effects, suitable even for medically fragile patients. Individualized dosing can optimize benefits while minimizing adverse events. Exploring diverse treatment approaches, particularly in patients with limited life expectancy or high disease burden, could improve outcomes. Ongoing research is investigating alternative therapies and combinations to broaden treatment options. Combining bevacizumab with PARPi may be justified for first-line and recurrent maintenance therapy. Regardless of mutational status, PARPi should be considered for maintenance therapy in newly diagnosed advanced OC. Platinum sensitivity remains crucial for treatment decisions and predicting survival outcomes.
PubMed: 38931448
DOI: 10.3390/ph17060778 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Nanoscale ultrasound contrast agents have attracted considerable interest in the medical imaging field for their ability to penetrate tumor vasculature and enable...
Nanoscale ultrasound contrast agents have attracted considerable interest in the medical imaging field for their ability to penetrate tumor vasculature and enable targeted imaging of cancer cells by attaching to tumor-specific ligands. Despite their potential, traditional chemically synthesized contrast agents face challenges related to complex synthesis, poor biocompatibility, and inconsistent imaging due to non-uniform particle sizes. To address these limitations, bio-synthesized nanoscale ultrasound contrast agents have been proposed as a viable alternative, offering advantages such as enhanced biocompatibility, consistent particle size for reliable imaging, and the potential for precise functionalization to improve tumor targeting. In this study, we successfully isolated cylindrical gas vesicles (GVs) from and subsequently introduced the GVs-encoding gene cluster into using genetic engineering techniques. We then characterized the contrast imaging properties of two kinds of purified GVs, using in vitro and in vivo methods. Our results demonstrated that naturally isolated GVs could produce stable ultrasound contrast signals in murine livers and tumors using clinical diagnostic ultrasound equipment. Additionally, heterologously expressed GVs from gene-engineered bacteria also exhibited good ultrasound contrast performance. Thus, our study presents favorable support for the application of genetic engineering techniques in the modification of gas vesicles for future biomedical practice.
PubMed: 38931421
DOI: 10.3390/ph17060755 -
Pharmaceuticals (Basel, Switzerland) May 2024Nanotechnology has emerged as a transformative force in oncology, facilitating advancements in site-specific cancer therapy and personalized oncomedicine. The... (Review)
Review
Nanotechnology has emerged as a transformative force in oncology, facilitating advancements in site-specific cancer therapy and personalized oncomedicine. The development of nanomedicines explicitly targeted to cancer cells represents a pivotal breakthrough, allowing the development of precise interventions. These cancer-cell-targeted nanomedicines operate within the intricate milieu of the tumour microenvironment, further enhancing their therapeutic efficacy. This comprehensive review provides a contemporary perspective on precision cancer medicine and underscores the critical role of nanotechnology in advancing site-specific cancer therapy and personalized oncomedicine. It explores the categorization of nanoparticle types, distinguishing between organic and inorganic variants, and examines their significance in the targeted delivery of anticancer drugs. Current insights into the strategies for developing actively targeted nanomedicines across various cancer types are also provided, thus addressing relevant challenges associated with drug delivery barriers. Promising future directions in personalized cancer nanomedicine approaches are delivered, emphasising the imperative for continued optimization of nanocarriers in precision cancer medicine. The discussion underscores translational research's need to enhance cancer patients' outcomes by refining nanocarrier technologies in nanotechnology-driven, site-specific cancer therapy.
PubMed: 38931344
DOI: 10.3390/ph17060677